E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post surgery pain management |
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E.1.1.1 | Medical condition in easily understood language |
Management of pain after surgery |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036237 |
E.1.2 | Term | Post operative analgesia |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056350 |
E.1.2 | Term | Pain management |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036286 |
E.1.2 | Term | Post-operative pain |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain following three types of major surgery (cardiac, thoracic and abdominal). The hypothesis to be tested is that gabapentin reduces opioid use after surgery and speeds up recovery, thereby reducing post-operative hospital stay compared to standard multimodal analgesia (usual care). Hence, the primary outcome is the time from start of surgery to hospital discharge. Post-operative hospital stay has been chosen because it will reflect the anticipated earlier recovery with gabapentin. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcomes have been selected to assess the efficacy and safety of gabapentin and include: 1) Opioid consumption in the period from surgery until hospital discharge; 2) Opioid consumption from discharge until 4 months; 3) Acute post-operative pain assessed using the numerical rating scale (NRS) completed at 1 hr, 4 hr, 12 hr post-surgery and then twice daily to discharge; 4) Adverse health events from randomisation to discharge and serious adverse events up to 4 months; 5) HRQoL measured using the EQ-5D 5 level questionnaire and Short-form (SF) 12 completed at baseline and at follow-up at approximately 4 weeks and 4 months; 6) Resource use to 4 months (measured during the hospital stay, at 4 weeks and 4 months); 7) Pain measured at baseline, at 4 weeks and at 4 months using the Brief Pain Inventory (BPI). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participant may enter study if ALL of the following apply:
1. Over 18 years of age; 2. Undergoing non-emergency surgery: - Cardiac (surgery on the heart and great vessels carried out via midline sternotomy); - Thoracic surgery (open or minimal access surgery on the lungs and surrounding tissues); - Abdominal (open or minimal access surgery within the abdominal cavity); 3. Expected to stay in hospital at least until day 2 after surgery (day 0 is day of surgery). 4. Expected to be able to swallow during the time of the study intervention. |
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E.4 | Principal exclusion criteria |
Participants may not enter study (i.e. may not be randomised) if ANY of the following apply:
1. Taking anti-epileptic medication(s); 2. Allergy to gabapentin; 3. Already taking gabapentin or gabapentanoids; 4. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption; 5. Planned epidural analgesia; 6. Intended use of any gabapentanoids in the peri-operative analgesic protocol other than the study medication (this includes but is not restricted to: pregabalin, enacarbil gabapentin, 4-methylpregabalin and phenibut); 7. Known renal impairment (for such patients, estimated glomerular filtration rate (eGFR) <30ml/min/1.732); 8. Weight <50kg; 9. Inability to provide written informed consent to participate in the trial; 10. Unwilling to participate in follow-up; 11. Prisoners; 12. Enrolled in another clinical trial and: a) the patient is currently taking an investigational medicinal product as part of the other trial; or b) co-enrolment is not permitted by the other trial; or c) co-enrolment would be burdensome for the patient. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is the time from start of surgery to hospital discharge. Post-operative hospital stay has been chosen because it will reflect the anticipated earlier recovery with gabapentin. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary outcome will be the time from start of surgery to hospital discharge. |
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E.5.2 | Secondary end point(s) |
Secondary outcomes have been selected to assess the efficacy and safety of gabapentin and include: 1) Opioid consumption in the period from surgery until hospital discharge; 2) Opioid consumption from discharge until 4 months; 3) Acute post-operative pain assessed using the numerical rating scale (NRS) completed at 1 hr, 4 hr, 12 hr post-surgery and then twice daily to discharge; 4) Adverse health events from randomisation to discharge and serious adverse events up to 4 months; 5) HRQoL measured using the EQ-5D 5 level questionnaire and Short-form (SF) 12 completed at baseline and at follow-up at approximately 4 weeks and 4 months; 6) Resource use to 4 months (measured during the hospital stay, at 4 weeks and 4 months); 7) Pain measured at baseline, at 4 weeks and at 4 months using the Brief Pain Inventory (BPI).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time points of evaluation of secondary outcomes: 1) Opioid consumption in the period from surgery until hospital discharge; 2) Opioid consumption from discharge until 4 months; 3) Acute post-operative pain assessed using the numerical rating scale (NRS) completed at 1 hr, 4 hr, 12 hr post-surgery and then twice daily to discharge; 4) Adverse health events from randomisation to discharge and serious adverse events up to 4 months; 5) HRQoL measured using the EQ-5D 5 level questionnaire and Short-form (SF) 12 completed at baseline and at follow-up at approximately 4 weeks and 4 months; 6) Resource use to 4 months (measured during the hospital stay, at 4 weeks and 4 months); 7) Pain measured at baseline, at 4 weeks and at 4 months using the brief pain inventory (BPI). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Effectiveness and cost-effectiveness |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will end for a participant after they have completed follow up at 4-month post randomisation. The end of the trial as a whole will be after all trial participants have completed follow up, all data queries have been resolved, the database locked and the analysis completed. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 31 |